Study on the anti-depressant effects of Xiaoyao pill in a rate model of CUMS based on BDNF/HPA mechanism
Objective:To investigate the antidepressant effect and mechanism of Xiaoyao pill on CUMS rat model.Methods:Male Wistar rats were randomly divided into control group,model group,amnripoyline group,Xiaoyao pill group,and the CUMS model was established by using chronic mild and unpredictable stress for 4 weeks.The successfully modeled mice in the medication groups were intragastrically administered with the corresponding drugs.The effect of Xiaoyao pill on behavior in CUMS rats were observed by experiments of sucrose preference test(SPT),open field test(OFT),forced swim test(FST)and morris water maze test.The levels of HPA hormones and BDNF,TrkB and CREB were measured by ELISA.The mRNA and protein expressions of cortex and hippocampal BDNF,TrkB,CREB,and GR were determined by RT-PCR and Western-Blot methods.Results:Compared with the model group,the sugar-water preference rate,and the exercise time,distance and number of standing in the OFT were significantly higher in Xiaoyao pill group.The immobility time and the escape latency in morris water maze were significantly decreased.The swimming time and distance in the quadrant where the original platform was located were significantly increased.In addition,Xiaoyao pill significantly up-regulated the levels of BDNF,TrkB,and CREB and promoted CREB phosphorylation.It also decreased the levels of adrenal index,Cort,CRH,and ACTH,as well as decreased the level of GR expression in CUMS rats.Conclusion:Xiaoyao pill can improve depressive behavior in CUMS-induced rats,which may be related to the inhibition of HPA axis hyperfunction and the upregulation of BDNF function.The study provides pharmacological basis for clinical application.